Blood processing systems and methods which optically monitor incremental platelet volumes in a plasma constituent

ABSTRACT

Blood processing systems and methods separate blood into constituents including a plasma constituent that includes a platelet volume. The systems and methods detect the optical density of the plasma constituent and generate a first output indicative of the optical density. A processing element integrates the first output relative to the volume of plasma constituent and generates an integrated output. The integrated output correlates to the platelet volume. A second processing element generates an output based, at least in part, upon the integrated output, which comprises a value indicating a blood volume that needs be processed to obtain a desired platelet volume.

RELATED APPLICATION

This application is a continuation-in-part of U.S. patent applicationSer. No. 09/382,893, entitled “Blood Processing Systems and MethodsWhich Optically Derive the Volume of Platelets Contained in a PlasmaConstituent,” filed Aug. 25, 1999, now U.S. Pat. No. 6,183,651, which isa continuation in part of U.S. patent application Ser. No. 08/807,820,filed Feb. 26, 1997, now U.S. Pat. No. 5,833,866, and entitled “BloodCollection Systems and Methods Which Derive Instantaneous BloodComponent Yield Information During Blood Processing,” which is acontinuation of U.S. patent application Ser. No. 08/472,748, filed Jun.7, 1995 of the same title and now abandoned.

FIELD OF THE INVENTION

The invention relates to centrifugal processing systems and apparatus.

BACKGROUND OF THE INVENTION

Today, people routinely separate whole blood by centrifugation into itsvarious therapeutic components, such as red blood cells, platelets, andplasma.

Certain therapies transfuse large volumes of blood components. Forexample, some patients undergoing chemotherapy require the transfusionof large numbers of platelets on a routine basis. Manual blood bagsystems simply are not an efficient way to collect these large numbersof platelets from individual donors.

On line blood separation systems are today used to collect large numbersof platelets to meet this demand. On line systems perform the separationsteps necessary to separate concentration of platelets from whole bloodin a sequential process with the donor present. On line systemsestablish a flow of whole blood from the donor, separate out the desiredplatelets from the flow, and return the remaining red blood cells andplasma to the donor, all in a sequential flow loop.

Large volumes of whole blood (for example, 2.0 liters) can be processedusing an on line system. Due to the large processing volumes, largeyields of concentrated platelets (for example, 4×10¹¹ plateletssuspended in 200 ml of fluid) can be collected. Moreover, since thedonor's red blood cells are returned, the donor can donate whole bloodfor on line processing much more frequently than donors for processingin multiple blood bag systems.

Nevertheless, a need still exists for further improved systems andmethods for collecting cellular-rich concentrates from blood componentsin a way that lends itself to use in high volume, on line bloodcollection environments, where higher yields of critically neededcellular blood components like platelets can be realized.

As the operational and performance demands upon such fluid processingsystems become. more complex and sophisticated, the need exists forautomated process controllers that can gather and generate more detailedinformation and control signals to aid the operator in maximizingprocessing and separation efficiencies.

SUMMARY OF THE INVENTION

The invention provides blood processing systems and methods whichseparate blood into constituents including a plasma constituent havingan optical density. The systems and methods convey a volume of theplasma constituent through an outlet path, while detecting the opticaldensity of the plasma constituent. The systems and methods generate afirst output indicative of the detected optical density. The systems andmethods integrate the first output relative to the volume of plasmaconstituent conveyed to generate an integrated output. The integratedoutput correlates to the platelet volume carried in the plasmaconstituent and obviates the need to otherwise obtain the plateletvolume by off line counting and sizing techniques. The systems andmethods generate a second output based, at least in part, upon theintegrated opacity value, comprising a value indicating a blood volumethat needs be processed to obtain a desired platelet volume.

In a preferred embodiment, the plasma constituent includes a lipidcontent. In this embodiment, the systems and methods adjust the firstoutput in proportion to the lipid content.

In a preferred embodiment, the systems and methods generate a thirdoutput based, at least in part, upon the integrated output. In apreferred embodiment, the third output comprises parameters for storingthe platelet volume contained within the plasma constituent. Forexample, the third output can include a value representing the number ofselected storage containers to be used for the platelet volume, or avalue representing the recommended volume of storage medium for theplatelet volume.

The various aspects of the invention are especially well suited for online blood separation processes.

Features and advantages of the inventions are set forth in the followingDescription and Drawings, as well as in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevation view, with portions broken away and insection, of a blood processing system comprising a centrifuge with aninterface detection system, which embodies features of the invention,the bowl and spool of the centrifuge being shown in their operatingposition;

FIG. 2 is a side elevation view, with portions broken away and insection, of the centrifuge shown in FIG. 1, with the bowl and spool ofthe centrifuge shown in their upright position for receiving a bloodprocessing chamber;

FIG. 3 is a top perspective view of the spool of the centrifuge shown inFIG. 2, in its upright position and carrying the blood processingchamber;

FIG. 4 is a plan view of the blood processing chamber shown in FIG. 3,out of association with the spool;

FIG. 5 is an enlarged perspective view of the interface ramp carried bythe centrifuge in association with the blood processing chamber, showingthe centrifugally separated red blood cell layer, plasma layer, andinterface within the chamber when in a desired location on the ramp;

FIG. 6 is an enlarged perspective view of the interface ramp shown inFIG. 5, showing the red blood cell layer and interface at an undesiredhigh location on the ramp;

FIG. 7 is an enlarged perspective view of the interface ramp shown inFIG. 5, showing the red blood cell layer and interface at an undesiredlow location on the ramp;

FIG. 8 is a side perspective view of the bowl and spool of thecentrifuge when in the operating position, showing the viewing head,which forms a part of the interface controller, being carried by thecentrifuge to view the interface ramp during rotation of the bowl;

FIG. 9 is a perspective view of the viewing head, with portions brokenaway and in section, showing the light source and light detector, whichare carried by the viewing head, in alignment with the interface ramp,as viewed from within the spool and bowl of the centrifuge;

FIG. 10 is a side section view of the bowl, spool, and viewing head whenthe viewing head is aligned with the interface ramp;

FIG. 11 is a schematic view of the interface processing element and theinterface command element, which form a part of the interfacecontroller;

FIG. 12 is a schematic view of the signal converting element, whichforms a part of the interface processing element shown in FIG. 11;

FIG. 13 shows, in its upper portion, a voltage signal generated by theviewing head when passing along the interface ramp and, in its lowerportion, a square waveform, which the processing element of theinterface controller generates from the voltage signal for the purposeof analyzing the location of the interface on the ramp;

FIG. 14 is a schematic view of the blood calibration element, whichforms a part of the interface controller;

FIG. 15 is a schematic view of the first and second utility functions ofthe processing control application, which forms a part of the bloodprocessing system shown in FIG. 1, as well as the associated monitorwhich optically monitors the opacity of PRP transported from theseparation chamber;

FIG. 16 is a plot showing the fluctuations in the opacity of fluidmonitored by the optical monitor shown in FIG. 15, which constitutes aninput to the first utility function also shown schematically in FIG. 15;

FIG. 17 is a plot showing the correlation of the integrated opticaldensity value derived by the first utility function, shown in FIG. 15,to collected platelet volume data;

FIG. 18 is a plot showing the correlation of the integrated opticaldensity value derived by the first utility function, shown in FIG. 15,to platelet yield data;

FIG. 19 is a graph showing the relationship between the partial pressureof oxygen and the permeation of a particular storage container, whichthe second utility function shown in FIG. 15 takes into account inrecommending optimal storage parameters in terms of the number ofstorage containers; and

FIG. 20 is a graph showing the relationship between the consumption ofbicarbonate and storage thrombocytocrit for a particular storagecontainer, which the second utility function shown in FIG. 15 takes intoaccount in recommending optimal storage parameters in terms of thevolume of plasma storage medium.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIGS. 1 and 2 show a blood processing system 10, which incorporates aninterface controller 12 that embodies features of the invention. Theinvention is described in the context of blood processing, because it iswell suited for use in this environment. Still, it should be appreciatedthat use of the invention is not limited to blood processing. Thefeatures of the invention can be used in association with any system inwhich materials that can be optically differentiated are handled.

A. The Centrifuge

The system 10 includes a centrifuge 14 used to centrifugally separateblood components. In the illustrated embodiment, the centrifuge 14separates whole blood to harvest red blood cells (RBC), plateletconcentrate (PC), and platelet-poor plasma (PPP). The centrifuge 14 canalso be used to harvest mononuclear cells and granulocytes from blood.

The centrifuge 14 is of the type shown in U.S. Pat. No. 5,316,667, whichis incorporated herein by reference. The centrifuge comprises a bowl 16and a spool 18 . The bowl 16 and spool 18 are pivoted on a yoke 20between an upright position, as FIG. 2 shows, and a suspended position,as FIG. 1 shows.

When upright, the spool 18 can be opened by movement at least partiallyout of the bowl 16, as FIG. 2 shows. In this position, the operatorwraps a flexible blood processing chamber 22 (see FIG. 3) about thespool 18. Closure of the spool 18 and bowl 16 encloses the chamber 22for processing. When closed, the spool 18 and bowl 16 are pivoted intothe suspended position for rotation about an axis.

B. The Blood Processing Chamber

The blood processing chamber 22 can be variously constructed. FIG. 4shows a representative preferred embodiment.

The chamber 22 shown in FIG. 4 provides multi-stage processing. A firststage 24 separates WB into RBC and platelet-rich plasma (PRP). A secondstage 26 separates the PRP into PC and PPP.

As FIGS. 3 and 4 best show, a port 28 conveys WB into the first stage24. Ports 30 and 32, respectively, convey PRP and RBC from the firststage 24. RBC is returned to the donor. A port 34 conveys PRP into thesecond stage 26. A port 36 conveys PPP from the second stage 26, leavingPC in the second stage 26 for resuspension and transfer to one or morestorage containers. The ports 28, 30, 32, 34, and 36 are arrangedside-by-side along the top transverse edge of the chamber 22.

As FIGS. 1 and 3 best show, a tubing umbilicus 38 is attached to theports 28, 30, 32, 34, and 36. The umbilicus 38 interconnects the firstand second stages 24 and 26 with each other and with pumps and otherstationary components located outside the rotating components of thecentrifuge 14 (not shown). As FIG. 1 shows, a non-rotating (zero omega)holder 40 holds the upper portion of the umbilicus 38 in a non-rotatingposition above the suspended spool 18 and bowl 16. A holder 42 on theyoke 20 rotates the mid-portion of the umbilicus 38 at a first (oneomega) speed about the suspended spool 18 and bowl 16. Another holder 44(see FIG. 2) rotates the lower end of the umbilicus 38 at a second speedtwice the one omega speed (the two omega speed), at which the suspendedspool 18 and bowl 16 also rotate. This known relative rotation of theumbilicus 38 keeps it untwisted, in this way avoiding the need forrotating seals.

As FIG. 4 shows, a first interior seal 46 is located between the PRPcollection port 30 and the WB inlet port 28. A second interior seal 48is located between the WB inlet port 28 and the RBC collection port 32.The interior seals 46 and 48 form a WB inlet passage 50 and a PRPcollection region 52 in the first stage 24. The second seal 48 alsoforms a RBC collection passage 54 in the first stage 24.

The WB inlet passage 50 channels WB directly into the circumferentialflow path immediately next to the PRP collection region 52. As shown inFIG. 5, the WB separates into an optically dense layer 56 of RBC, whichforms as RBC move under the influence of centrifugal force toward thehigh-G wall 62. The movement of RBC 56 displaces PRP radially toward thelow-G wall 64, forming a second, less optically dense layer 58.

Centrifugation of WB also forms an intermediate layer 60, also calledthe interface, which constitutes the transition between the formedcellular blood components and the liquid plasma component. RBC typicallyoccupy this transition region. White blood cells may also occupy thistransition region.

Platelets, too, can leave the PRP layer 58 and settle on the interface60. This settling action occurs when the radial velocity of the plasmanear the interface 60 is not enough to keep the platelets suspended inthe PRP layer 58. Lacking sufficient radial flow of plasma, theplatelets fall back and settle on the interface 60. Larger platelets(greater than about 30 femtoliters) are particularly subject to settlingon the interface 60. However, the closeness of the WB inlet region 50 tothe PRP collection region 52 in the chamber 22 shown in FIG. 4 createsstrong radial flow of plasma into the PRP collection region 52. Thestrong radial flow of plasma lifts platelets, large and small, from theinterface 60 and into the PRP collection region 52.

Further details of the separation chamber 22 are not material to theinvention and can be found in U.S. Pat. No. 5,316,667, previouslymentioned.

C. The Interface Controller

As FIG. 5 shows, a ramp 66 extends from the high-G wall 62 of the bowl16 at an angle across the PRP collection region 52. The angle, measuredwith respect to the axis of the PRP collection port 30 is preferablyabout 30°. FIG. shows the orientation of the ramp 66 when viewed fromthe low-G wall 64 of the spool 18. FIG. 4 shows, in phantom lines, theorientation of the ramp 66 when viewed from the high-G wall 62 of thebowl 16.

Further details of the angled relationship of the ramp 66 and the PRPcollection port 30 are not material to the invention. They can be foundin U.S. patent application Ser. No. 08/472,561, filed Jun. 7, 1995, nowU.S. Pat. No. 5,833,866, and entitled “Enhanced Yield Blood ProcessingSystem with Angled Interface Control Surface,” which is incorporatedherein by reference.

The ramp 66 forms a tapered wedge that restricts the flow of fluidtoward the PRP collection port 30. The top edge of the ramp 66 extendsto form a constricted passage 68 along the low-G wall 64. PRP must flowthrough the constricted passage 68 to reach the PRP collection port 30.

As FIG. 5 shows, the ramp 66 diverts the fluid flow along the high-Gwall 62. This flow diversion changes the orientation of the interface 60between the RBC layer 56 and the PRP layer 58 within the PRP collectionregion 52. The ramp 66 thereby displays the RBC layer 56, PRP layer 58,and interface 60 for viewing through the low-G wall 64 of the chamber22.

The interface controller 12 includes a viewing head 70 (see FIGS. 1 and8) carried on the yoke 20. The viewing head 70 is oriented to opticallyview the transition in optical density between the RBC layer 56 and thePRP layer 58 on the ramp 66. The interface controller 12 also includes aprocessing element 72 (see FIGS. 11 and 13), which analyzes the opticaldata obtained by the viewing head 70 to derive the location of theinterface 60 on the ramp 66 relative to the constricted passage 68.

The location of the interface 60 on the ramp 66 can dynamically shiftduring blood processing, as FIGS. 6 and 7 show. The interface controller12 includes a command element 74 (see FIGS. 11 and 13), which varies therate at which PRP is drawn from the chamber 22 to keep the interface 60at a prescribed location on the ramp 66 (which FIG. 5 shows).

Maintaining the interface 60 at a prescribed location on the ramp 66 isimportant. If the location of the interface 60 is too high (that is, ifit is too close to the constricted passage 68 leading to the PRPcollection port 30, as FIG. 6 shows), RBC, and, if present, white bloodcells can spill over and into the constricted passage 68, adverselyaffecting the quality of PRP. On the other hand, if the location of theinterface 60 is too low (that is, if it resides too far away from theconstricted passage 68, as FIG. 7 shows), the fluid dynamicsadvantageous to effective platelet separation can be disrupted.Furthermore, as the distance between the interface 60 and theconstricted passage 68 increases, the difficulty of drawing largerplatelets into the PRP flow increases. As a result, a distant interfacelocation results in collection of only the smallest platelets, andoverall platelet yield will, as a consequence, be poor.

(1) The Interface Viewing Head

Referring to FIGS. 8 to 10, the viewing head 70, carried by the yoke 20,includes a light source 76, which emits light that is absorbed by RBC.In the illustrated and preferred embodiment, the light source 76includes a circular array of red light emitting diodes 80. Of course,other wavelengths absorbed by RBC, like green or infrared, could beused.

In the illustrated embodiment, seven light emitting diodes 80 comprisethe light source 76. More diodes 80 may be used, or fewer diodes 80 canbe used, depending upon the optical characteristics desired.

The viewing head 70 also includes a light detector 78 (see FIGS. 9 and10), which is mounted adjacent to the light source 76. In theillustrated and preferred embodiment, the light detector 78 comprises aPIN diode detector, which is located generally in the geometric centerof the circular array of light emitting diodes 80.

The yoke 20 and viewing head 70 rotate at a one omega speed, as thespool 18 and bowl 16 rotate at a two omega speed. The light source 76directs light onto the rotating bowl 16. In the illustrated embodiment(see FIG. 8), the bowl 16 is transparent to the light emitted by thesource 76 only in the region 82 where the bowl 16 overlies the interfaceramp 66. In the illustrated embodiment, the region 82 comprises a windowcut out in the bowl 16. The remainder of the bowl 16 that lies in thepath of the viewing head 70 comprises a light absorbing material.

The interface ramp 66 is made of a light transmissive material. Thelight from the source 76 will thereby pass through the transparentregion 82 of the bowl 16 and the ramp 66 every time the rotating bowl 16and viewing head 70 align. The spool 18 may also carry a lightreflective material 84 behind the interface ramp 66 to enhance itsreflective properties. The spool 18 reflects incoming light receivedfrom the source 76 out through the transparent region 82 of the bowl 16,where it is sensed by the detector 78. In the illustrated embodiment,light passing outward from the source 76 and inward toward the detector78 passes through a focusing lens 120 (shown in FIGS. 9 and 10), whichforms a part of the viewing head 70.

The arrangement just described optically differentiates the reflectiveproperties of the interface ramp 66 from the remainder of the bowl 16.This objective can be achieved in other ways. For example, the lightsource 76 could be gated on and off with the arrival and passage of theramp 66 relative to its line of sight. As another example, the bowl 16outside the transparent region 82 could carry a material that reflectslight, but at a different intensity than the reflective material 84behind the interface ramp 66.

As the transparent interface region 82 of the bowl 16 comes intoalignment with the viewing head 70, the detector 78 will first senselight reflected through the plasma layer 58 on the ramp 66. Eventually,the RBC layer 56 adjacent the interface 60 on the ramp 66 will enter theoptical path of the viewing head 70. The RBC layer 56 absorbs light fromthe source 76 and thereby reduces the previously sensed intensity of thereflected light. The intensity of the reflected light sensed by thedetector 78 represents the amount of light from the source 76 that isnot absorbed by the RBC layer 56 adjacent to the interface 60.

(2) The Interface Processing Element As FIG. 11 shows, the interfaceprocessing element 72 includes a signal converting element 112, whichconverts the sensed light intensity output of the detector 78 (acurrent) to an amplified voltage signal.

As FIG. 12 shows, the signal converting element 112 includes aninverting current to voltage (I/V) amplifier 114, which converts therelatively low positive current signal from the detector 78 (typically,in μA) to an amplified negative voltage signal. The current-to-voltagegain of the amplifier 114 can vary. In a representative embodiment, thegain is on the order of 58,000, so that current of, for example, 1 μA isconverted to a voltage signal of −58 mV. A non-inverting voltageamplifier (V/V) 116 further amplifies the negative voltage signal (inmV) to a negative voltage signal (in V) (i.e., a gain of about 400).This twice amplified negative voltage signal is passed through a buffer118. The output of the buffer 118 constitutes the output of the signalconverting element 112. In the illustrated embodiment, the totalamplification factor (from detector current signal to processed negativevoltage signal) is about 23 million.

FIG. 13 shows in solid lines a representative curve (designated V1),which plots representative negative voltage outputs of the signalconverting element 112 for light signals detected when a lighttransmissive liquid, e.g., saline, resides along the entire length ofthe ramp 66. The curve V1 shows the region 88 where the light signaldetected increase, level out, and then decrease, as the transparentregion 82 and viewing head 70 pass into and out of alignment. In theillustrated embodiment, the voltage curve V1 is negative-going forincreasing light signals, due to processing by the signal convertingelement 112. It should be appreciated that the light signals could beprocessed to provide a non-inverted voltage output, so that the voltagecurve V1 would be positive-going for increasing light signals.

Referring back to FIG. 11, a waveshaping element 90 converts theamplified voltage signals to a square wave time pulse. In theillustrated embodiment, the element 90 comprises a voltage comparator,which receives as input the amplified voltage signals and a selectedthreshold value (THRESH). The output of the voltage comparator 88 is one(1) when the voltage signal lies below THRESH (that is, when the voltagesignal lies further from zero than THRESH) and zero (0) when the voltagesignal lies above THRESH (that is, when the voltage signal lies closerto zero than THRESH).

In the illustrated embodiment, THRESH comprises a digital number between0 and 4095. The digital number is converted by a 12 bitdigital-to-analog converter 120 to a voltage analog value between +10and −10. For example, a digital number of zero (0) for THRESH representsan analog output of +10V, while a digital number of 4095 for THRESHrepresents an analog output of −10V.

FIG. 13 shows in solid lines a representative square wave pulse(designated P1) processed by the comparator 90 from the voltage curveV1, based upon a selected value for THRESH. Negative-going voltage curveV1 varies from zero (0) (when no light is sensed by the detector 70) to−13.5 V (when maximum light is sensed by the detector 70), and THRESH isthe digital number 3481, which the converter 120 converts to an analogvoltage value of −7V. The square wave pulse P1 has a width (designatedW1 in FIG. 13) expressed in terms of time. The width W1 is proportionalto the time that a light signal below THRESH is detected (that is, whenthe negative voltage signal is farther from zero (0) than analog voltagevalue of THRESH).

As FIG. 13 shows, maximum light is detected (negative-going voltagesignal at −13.5 V) when the interface viewing region 82 and the viewinghead 70 align. When a light transmissive material like saline residesalong the entire interface ramp 66, the width W1 of the square wavepulse P1 is proportional to the entire time period that the interfaceviewing region 82 and viewing head 70 align. Width W1 will also becalled the baseline pulse width, or BASE.

When material having a high-relative light absorption properties, suchas RBC, occupies a portion of the ramp 66, the profile of the sensedvoltages changes. FIG. 13 shows in phantom lines a representative curve(designated V2), which plots representative processed voltage signalsdetected when RBC occupy about 70% of the length of the ramp 66.Negative-going voltage curve V2 varies from zero (0) (when no light issensed by the detector 70) to −9.9 V (when maximum light is sensed bythe detector 70). The curve V2 follows the path of V1 until the detector78 senses the plasma layer 58, which is not a transmissive to light assaline. The maximum sensed signal intensity for plasma (I2 _(PLASMA))(for example, −9.9 V) is therefore less than maximum sensed signalintensity for saline (I1 _(SALINE)) (for example −13.5 volts). The timeperiod during which I2 _(PLASMA) exists is also significantly shorterthan the time period which I1 _(SALINE) exists. Curve V2 shows thegradual decrease in the sensed voltage signal as the light absorbing RBClayer 56 comes progressively into the field of view of the head 70(which is generally designated I2 _(RBC) in FIG. 13). Curve V2eventually joins the path of curve V1, as the transparent region 82 andviewing head 70 pass out of alignment.

FIG. 13 also shows in phantom lines that the relative width (W2) ofsquare wave pulse (P2), processed by the comparator 90 using the sameTHRESH as P1, shortens. The width (W2) diminishes in proportion to thewidth of the RBC layer 56 relative to the width of the plasma layer 58on the ramp. As the RBC layer 56 occupies more of the ramp 66, i.e., asthe RBC-plasma interface 60 moves closer to the constricted passage 68,the pulse Width (W2) shortens relative to the baseline pulse width (W1),and vice versa.

Thus, and by comparing the width of a given pulse wave (such as W2)relative to the baseline pulse width (W1), the interface processingelement 72 assesses the relative physical location of the interface 60on the ramp 66.

As FIG. 11 shows, the interface processing element 72 includescalibration modules 92 and 94 to assure that the optically derivedphysical location of the interface 66 accurately corresponds with theactual physical location of the interface 66. The first calibrationmodule 92, also called the system calibration module, takes into accountthe geometry of the spool 18 and ramp 66, as well as operationalconditions that can affect the optical acquisition of interfaceinformation. The second calibration module 94, also called the bloodcalibration module, takes into account the physiology of the donor'sblood, in terms of the optical density of his or her plasma.

(i) System Calibration Module

The nominal value of the baseline pulse width BASE (expressed in unitsof time) is selected for a given system. In a representative embodiment,a value of, for example, 640 μsec can be selected for BASE. BASE (inmicroseconds) is converted to a digital count value (COUNTS), asfollows: $\begin{matrix}{{COUNTS} = {\left( {\frac{BASE}{PERIOD}*{SCALE}} \right) + {THRESH}_{ZERO}}} & (1)\end{matrix}$

where

SCALE is a selected scale factor (which, in the illustrated embodiment,can be, for example, 80604);

THRESH_(ZERO) is the digital threshold number that represents an analogthreshold voltage output of zero (which, in the illustrated embodiment,is 2048); and

PERIOD is the period of rotation of the detector 70, based upon thespeed of rotation of the detector 70 (DETECTOR_(Ω)), calculated asfollows:${PERIOD} = {\left( \frac{60}{{DETECTOR}_{\Omega}} \right) \times 10^{6}}$

Once calculated for a given DETECTOR_(Ω), COUNTS need not berecalculated at different values of DETECTOR_(Ω), provided BASE is notchanged.

The system calibration module 92 derives a square pulse wave P_(SALINE),like P1 in FIG. 13, by conveying a light transmissive liquid, such assaline, through the chamber 22, while sampling voltage values along theramp 66. The voltage value samples are processed by the comparator 90 tocreate the square wave pulse P_(SALINE), using an estimated initialthreshold value THRESH_(START). The width W_(START) of the pulseP_(SALINE) formed using THRESH_(START) is measured and compared to thebaseline width BASE, which is determined according to Equation (1).

Moving THRESH closer to zero than THRESH_(START) will increase the pulsewidth, and vice versa. When W_(START) does not equal BASE, or,alternatively, if W_(START) falls outside a specified satisfactory rangeof values for BASE, the system calibration module 92 varies thethreshold value from THRESH_(START) to vary the pulse width, until thepulse width of P_(SALINE) meets the target criteria for BASE. Thethreshold value that achieves the target baseline pulse width BASEbecomes the default threshold value THRESH_(DEFAULT) for the system.

Despite the derivation of THRESH_(DEFAULT), variations in sensed pulsewidth can occur during normal use independent of changes in the actualphysical dimension of the interface. For example, sensed voltage signalscan change due to changes occurring within the viewing head 70, such asloss of focus, deposition of foreign materials on optical surfaces,shifts in optical alignment, or weakening of the light emitting diodes80 or detector 78. Sensed voltage signals will change due to degradationof optical performance, independent of and unrelated to changes in thephysical dimensions of the interface. When processed by the converter 90using THRESH_(DEFAULT), the changed voltage signals can result in areduced or enlarged pulse width, which may no longer accurately reflectthe actual state of the interface. Erroneous control signals may result.

In the illustrated and preferred embodiment, the system calibrationmodule 92 includes a set up protocol 96. The protocol 96 sets athreshold value THRESH to obtain the baseline pulse width BASE usingactual performance conditions existing at the beginning of eachprocessing cycle.

The set up protocol 96 commands the system to convey saline (or otherselected light transmissive material) through the separation chamber 22,as before described in connection with deriving THRESH_(DEFAULT). Arepresentative number of samples (e.g., 10 samples) of pulse widthsW_(DEFAULT(1 to n)) are obtained based upon sensed voltage values usingTHRESH_(DEFAULT). The sample pulse widths are averaged W_(DEFAULT(AVG))and compared to BASE for the system, derived according to Equation (1).If W_(DEFAULT(AVG)) equals BASE, or, alternatively, lies within anacceptable range of values for BASE, THRESH is set at THRESH_(DEFAULT).

In a representative implementation, the protocol 96 uses the followingcriteria is used to evaluate THRESH_(DEFAULT):

IF W_(DEFAULT(AVG))≧BASE_(LOWER) AND

W_(DEFAULT(AVG))≦BASE_(UPPER) THEN

THRESH=THRESH_(DEFAULT)

where:

BASE_(UPPER) is a selected maximum value for the baseline pulse width,e.g., BASE times a selected multiplier greater than 1.0, for example1.0025; and

BASE_(LOWER) is a selected minimum value for the baseline pulse width,e.g., BASE times a selected multiplier less than 1.0, for example0.9975.

If the W_(DEFAULT(AVG)) does not meet the above criteria, the set upprocedure searches for a value for THRESH that brings W_(DEFAULT(AVG))into compliance with the established criteria for BASE. Various searchalgorithms can be used for this purpose.

For example, the set up procedure can use a half-step search algorithm,as follows:

where THRESH is the name given to the interface threshold valueselected; THRESH_(UPPER) is a set maximum value for THRESH;THRESH_(LOWER) is a set minimum value for THRESH; and W_(SAMPLE(AVG)) isan average of pulse widths taken during a set sample period.

set THRESH_(n-1)=THRESH_(DEFAULT)

set THRESH_(UPPER)

set THRESH_(LOWER)

DO n=2 to 20

IF W_(SAMPLE(AVG))>BASE_(UPPER) THEN THRESH_(LOWER)=THRESH_(n-1)

THRESH_(n)=(THRESH_(LOWER)+THRESH_(UPPER))/2 ELSEIFW_(SAMPLE(AVG))<BASE_(LOWER) THEN THRESH_(UPPER)=THRESH_(n-1)

THRESH_(n)=(THRESH_(UPPER)+THRESH_(LOWER))/2 ELSIF end the search ENDIFEND DO

IF n=20 THEN Activate a Warning Alarm: Interface Detector Problem ENDIF

The system calibration module 92 thereby assures that the opticallyderived location of the interface 66 is not skewed based uponoperational conditions that can affect the optical acquisition. ofinterface information.

(ii) Blood Calibration Module

The interface controller 12 can operate on the premise the opticaldensity of the donor's plasma residing on the ramp 66 is substantiallyequivalent to the optical density of the material (e.g., saline) used bythe system calibration module 92 at the outset of a given procedure.Typically, the optical density of normal plasma can be consideredequivalent to saline.

However, the optical density of plasma will vary according to theconcentration of platelets carried in the plasma. Therefore, plasmaparticularly rich in platelets, which is a processing goal of the system10, has a density that differs significantly from saline or normalplasma.

The optical density of plasma will also vary according to theconcentration of lipids in the plasma, which depends upon the physiologyor morphology of the individual donor. Lipemic plasma has a density thatdiffers significantly from saline or non-lipemic plasma.

The presence of plasma on the ramp 66 carrying high concentrations ofplatelets or lipids, diminishes the magnitude of the sensed voltagesignals, independent of and unrelated to changes in the physicaldimensions of the interface. When processed by the converter 90 usingTHRESH, set by the system calibration module 92 just described, theassociated square wave pulses possess a reduced pulse width. The reducedpulse width is caused by the physiology of the donor's blood, and doesnot accurately reflect the actual state of the interface.

For example, a RBC-plasma interface 60 located at the proper position onthe ramp 66 will, in the presence of lipemic plasma or very plateletrich plasma, generate a pulse width, which is otherwise indicative fornormal plasma of an RBC-plasma interface 60 that is too close. Theartificially reduced pulse width will generate an error signal, whichcommands a reduction in the rate at which plasma is conveyed through theport 34. The previously properly positioned interface 60 is needlesslyshifted to an out-of-position location down the ramp 66.

The second calibration module 94 adjusts the pulse width in the presenceof plasma having an optical density significantly different than saline,to reflect the true position of the interface and thereby avoidblood-related optical distortions. The module 94 includes an opticalmonitor 98 (see FIG. 14), which senses the optical density of plasmaexiting the plasma outlet port 30 or entering the PRP inlet port 34. Inthe illustrated embodiment shown in FIG. 13, the optical monitor 98 is aconventional hemoglobin detector, used on the Autopheresis-C® bloodprocessing device sold by the Fenwal Division of Baxter HealthcareCorporation. The monitor 98 comprises a red light emitting diode 102,which emits light into the plasma outlet tubing 104. In thisarrangement, the wavelength for detecting the optical density of plasmais essentially the same as the wavelength for detecting the location ofthe interface. Of course, other wavelengths, like green or infrared,could be used. The monitor 98 also includes a PIN diode detector 106 onthe opposite side of the tubing 104.

Using the essentially the same wavelength for monitoring the interfaceand monitoring plasma is a preferred implementation. Using essentiallythe same wavelengths makes the absorbance spectrum for plasmaessentially the same for both detectors. Therefore, there is no need tocorrelate the absorbance spectrum of the interface detector to theabsorbance spectrum of the plasma detector. Of course, differentwavelengths can be used, if desired, in which case the absorbancespectrums for plasma of the different wavelengths should be correlated,to achieve accurate calibration results.

The second calibration module 94 also includes a-processing element 100,which receives signals from the monitor 98 to compute the opticaltransmission of the liquid conveyed through the tubing 104, which iscalled OPTTRANS. Various algorithms can be used by the processingelement 100 to compute OPTTRANS. In a representative embodiment,OPTTRANS is derived, as follows: $\begin{matrix}{{OPTTRANS} = \frac{{COR}\left( {{RED}\quad {SPILL}} \right)}{CORRREF}} & (2)\end{matrix}$

where COR(RED SPILL) is calculated as follows:

COR(RED SPILL)=RED-REDBKGRD

where:

RED is the output of the diode detector when the red light emittingdiode is on and the liquid flows through the tubing;

REDBKGRD is the output of the diode detector when the red light emittingdiode is off and the liquid flows through the tubing;

and where CORREF is calculated as follows:

CORREF=REF-REFBKGRD

where:

REF is the output of the red light emitting diode when the diode is on;and

REFBKGRD is the output of the red light emitting diode when the diode isoff.

Operating with the system calibration module 92, the processing element100 obtains data from the monitor 98 and derives the opticaltransmission of the tubing and the light transmissive, set up liquid,such as saline. In a preferred embodiment, optical transmission valuesare calculated at the fastest possible rate during the set up procedure.The values are averaged over the entire set up procedure to derive anoptical transmission value for the tubing and setup liquid(OPTTRANS_(SETUP)).

After set up is complete, and the system calibration module 92 is nolonger operative, the blood calibration module 92 continues duringsubsequent blood processing to derive the optical transmission of thetubing and plasma using Equation (2). In the preferred embodiment,optical transmission values are calculated by the processing element 100at the fastest possible rate during the blood processing procedure. Thevalues are periodically averaged at the end of a set sampling interval(for example, every 180 seconds) to derive an optical transmission valuefor the tubing and plasma (OPTTRANS_(PLASMA)).

At the end of each set sampling interval (i.e., every 180 seconds, forexample), the processing module 100 determines a new threshold valueTHRESH, for deriving the pulse width, which varies as a function ofOPTRANS, as follows: $\begin{matrix}{{THRESH} = {{THRESH}_{n} - {\left\lbrack \frac{1 - {OPTRANS}_{PLASMA}}{{OPTRANS}_{SETUP}} \right\rbrack*{MULT}}}} & (3)\end{matrix}$

where MULT is a predetermined scale factor from 0 to, for example, 1000.In the illustrated embodiment, MULT can be set at 200.

The foregoing correction of THRESH increases the pulse width in relationto increases in optical density of plasma on the ramp 66. The secondcalibration module 94 thereby takes into account diminution in voltagesignal gain in the presence on the ramp 66 of lipemic plasma or plasmawith very high platelet counts. The second calibration module 94 therebyserves as a gain controller for the interface controller 12, adjustingthe width of the pulse to accurately reflect the actual physicallocation of the interface on the ramp, despite the presence of plasmahaving greater than normal optical density.

The interface processing element 72 ultimately outputs a signal, whichaccurately represents the interface location as a function of W. Forexample, when BASE=640 μsec, a measured pulse width W indicates that100% of the ramp 66 is occupied by plasma. A measured pulse width W of320 μsec indicates that plasma occupies 50% of the ramp 66, while ameasured pulse width W of 192 μsec indicates that plasma occupies 30% ofthe ramp 66 (i.e., RBC occupy 70% of the ramp 66), and so on.

The foregoing description shows the processing element 72 receivingsensed light intensity values from an interface detector 70 that senseslight reflected from the interface ramp 66. It should be appreciatedthat comparable light intensity values can be obtained for processing bythe processing element 72 from an interface detector that senses lightafter transmission through the interface ramp 66, without backreflection. In this alternative embodiment, a light source is carried bythe yoke 20 (in the same manner as the optical head 70), and a lightdetector is carried by the spool 18 behind the interface ramp 66, orvice versa.

(3) Interface Command Element

As FIG. 11 shows, the interface command element 74 receives as input theinterface location output of the processing element 72. The commandelement includes a comparator 108, which compares the interface locationoutput with a desired interface location to generate an error signal(E). The desired interface location is expressed as a control valueconsistent with the expression of the interface dimension output.

Generally speaking, for platelet collection, RBC should occupy no morethan about 60% to 65% of the ramp 66. This can conversely be expressedin terms of a control value (expressed as a percentage) of between 35%to 40% of BASE, meaning that the measured pulse width W should be 35% to40% of its maximum value. Alternatively, the control value can beexpressed in terms of a number representing a pulse width value (in timeunits) integrated to a voltage value proportional to the percentage ofplasma occupying the ramp 66.

Of course, different control values can be used depending upon theparticular blood component collection objectives.

When the control value is expressed in terms of a targeted RBCpercentage value, a positive error signal (+E) indicates that the RBClayer 56 on the ramp 66 is too large (as FIG. 6 shows). The interfacecommand element 74 generates a signal to reduce the rate which PRP isremoved through port 34. The interface 60 moves away from theconstricted passage 68 toward the desired control position (as FIG. 5shows), where the error signal (E) is zero.

A negative error signal (−E) indicates that the RBC layer 56 on the ramp66 is too small (as FIG. 7 shows). The interface command element 74generates a signal to increase the rate at which PRP is removed throughthe port 34. The interface 60 moves toward the constricted passage 68toward the desired control position (FIG. 5), where the error signal (E)is again zero.

The interface command element 74 can affect the rate at which plasma isremoved through the port 34 by controlling the relative flow rates ofWB, the RBC, and the PRP through their respective ports. In a preferredembodiment (as FIGS. 11 and 13 show), a pump 110 draws PRP via thetubing 104 through the port 34. The command element 74 controls the pumprate of the pump 110 to keep the interface 60 at the prescribed locationon the ramp 66, away from the constricted passage 68.

D. Optical Derivation of Platelet Volumes

As FIG. 15 shows, the system 10 preferably also includes a processingcontrol application 200, which comprises one or more utility functions,three of which, F1, F2, and F3 are shown. The one or more utilityfunctions F1, F2, and F3 provide processing status and parameterinformation and generate processing control variables for the system 10.The one or more utility functions F1, F2, and F3 are designed to achievespecified blood processing goals, taking into account the individualmorphology of the donor and actual conditions occurring as processingproceeds.

The number and type of utility functions can vary. For example, aparticular utility function can derive the yield of platelets during agiven processing session, estimate the processing time before commencinga given processing session and while the processing session is underway,or generate control variables that control the rate of citrateanticoagulant infusion during a given processing session. Examples ofutility functions are detailed in Brown U.S. Pat. No. 5,639,382,entitled “Systems and Methods for Deriving Recommended StorageParameters For Collected Blood Components” which is incorporated hereinby reference.

In the illustrated embodiment, the processing control application 200includes at least first, second, and third utility functions F1, F2, andF3. The first utility function F1 generates an optically derivedprocessing value, based upon on line monitoring of the opacity of thedonor's platelet-rich plasma (PRP) during processing. The opticallyderived processing value correlates with the volume of plateletscollected, and thereby obviates the need to calculate the plateletcollection volume based upon off line cell counting and sizingtechniques. The correlation between the optically derived processingvalue and the volume of platelets collected also obviates the need for acalibration factor to bring data derived on line into conformance withdate derived off line.

The second utility function F2 calculates optimal storage parameters forthe platelets collected, based in part upon the processing valueoptically derived by the first utility function F1. The second utilityfunction F2 specifies these parameters in terms of the number of storagecontainers and the volume of platelet-poor plasma (PPP) to use as aplatelet storage medium.

The third utility function F3 determines the amount of whole blood thatneeds to be processed to achieve a desired yield of platelets, based inpart upon the processing value optically derived by the first utilityfunction F1. F3 calculates this whole blood volume based upon theoptical transmission of PRP, which is normalized by a measuredtransmission of PPP, to take account of the lipid content of the donor'splasma.

(1) The Utility Function F1 The utility function F1 employs a processingelement 202 coupled to an optical monitor 204, which is positioned tosense the overall optical transmission of PRP separated from whole bloodin the first stage 24 of the chamber 22. This overall opticaltransmission value for PRP will be called T(PRP).

The processing element 202 calibrates the overall value T(PRP) against abaseline value, which will be called T (PPP). The baseline value T(PPP)reflects the optical transmission of the donor's plasma in the absenceof platelets, which also takes into account the lipid content of thedonor's plasma. The processing element 202 also preferably calibratesboth T(PRP) and T(PPP) against optical background “noise.”

Ultimately, the processing element 202 derives a calibrated opacityvalue, which reflects the opacity of the PRP due solely to the presenceof platelets.

The processing element 202 numerically integrates the calibrated opacityvalue relative to the plasma volume processed over time, to obtain anintegrated value, called PCI. It has been discovered that the magnitudeof PCI for a given procedure and donor, using a particular processingsystem, closely correlates to the platelet yield actually obtainedduring that procedure (expressed in units×10¹¹) and the volume ofplatelets actually collected during the procedure (expressed in ml). Asa result, neither of these actual values need be independentlycalculated by other means.

(i) The Optical Monitor

In the illustrated embodiment (see FIG. 15), the optical monitor 204 ispositioned along tubing 104 to sense the optical density of plasmaexiting the plasma outlet port 30 of the first stage 24 or entering thePRP inlet port 24 of the second stage 26. In the illustrated embodiment,the monitor 204 is located in line with the tubing 104 downstream of thePRP pump 110, previously described. Alternatively, the monitor 204 couldbe placed upstream of the PRP pump 110.

The optical monitor 204 can be constructed in various ways. In theillustrated embodiment shown in FIG. 15, the monitor 204 comprises aconventional hemoglobin detector, used, e.g., on the Autopheresis-C®blood processing device sold by the Fenwal Division of Baxter HealthcareCorporation. The monitor 204 comprises a red light emitting diode 206,which emits light into the plasma outlet tubing 104. Other wavelengths,like green or infrared, could be used.

The monitor 204 also includes a PIN diode detector 208 on the oppositeside of the tubing 104.

The wavelength for detecting the optical density of plasma can beessentially the same as the wavelength for detecting the location of theinterface, as previously described. In this way, the optical monitor 204serving the processing element 202 and the optical monitor 98 servingthe processing element 100(previously described and shown in FIGS. 11and 14) can comprise the same functional element.

(ii) Deriving a Calibrated Opacity Value

As liquid is conveyed through the tubing 104 from the first stage 24 tothe second stage 26, the processing element 202 receives signals fromthe monitor 204, indicative of the optical transmission of the liquid inthe tubing 104. When the liquid is PRP, the signals are indicative ofT(PRP), which varies as a function of the number and size of plateletsresiding in the PRP, as well as any background optical “noise” unrelatedto the opacity of the PRP. The processing element 202 takes thesefactors affecting the opacity signals into account to compute a PRPintensity value T(PRP).

Various algorithms can be used by the processing element to computeT(PRP). In a preferred embodiment, T(PRP) is calculated as follows:$\begin{matrix}{{T({PRP})} = \frac{{REDBKG} - {RED}}{{REFBKG} - {REF}}} & (4)\end{matrix}$

where:

RED represents the output of the diode detector 208 when the red lightemitting diode 206 is on and PRP flows through the tubing 104;

REDBKD is the output of the diode detector 208 when the red lightemitting diode 206 is off and PRP flows through the tubing 104;

REF is the output of the light emitting diode 206 when the diode 206 ison; and

REFBKG is the output of the light emitting diode 206 when the diode 206is off.

The values RED, REDBKG, REF, and REFBKG each comprises a digital numberbetween 0 (maximum light transmission) to 2048 (no light transmission).The digital number is obtained by converting the sensed light intensityoutput of the detector 208 (a current) into a negative voltage signalusing an inverting current to voltage (I/V) amplifier. The negativevoltage signal is further amplified, buffered, and processed in aconventional manner to provide the digital number output.

In the illustrated and preferred embodiment, the values RED, REDBKG,REF, and REFBKG are obtained by straight through transmission between asingle emitter 206 and a single detector 208 and include no side scattereffects.

In the illustrated embodiment, T(PRP) is sampled at a set sample period(the sample rate), e.g., once every five seconds.

(iii) Deriving Baseline T(PPP)

The T(PRP) signals also vary as a function of the lipid content of thedonor's plasma, in the manner previously described. In the illustratedembodiment, the processing element 202 takes the affect of the lipidcontent into account 202 by computing a PPP baseline intensity valueT(PPP), to yield a calibrated opacity value.

Various algorithms can be used by the processing element to computeT(PPP). In a preferred embodiment, T(PPP) is calculated in the samefashion as T(PRP), namely: $\begin{matrix}{{T({PPP})} = \frac{{REDBKG} - {RED}}{{REFBKG} - {REF}}} & \text{(4A)}\end{matrix}$

where:

RED represents the output of the diode detector 208 when the red lightemitting diode 206 is on and PPP flows through the tubing 104;

REDBKD is the output of the diode detector 208 when the red lightemitting diode 206 is off and PPP flows through the tubing 104;

REF is the output of the light emitting diode 206 when the diode 206 ison; and

REFBKG is the output of the light emitting diode 206 when the diode 206is off.

In the illustrated embodiment (see FIG. 15), platelet-poor plasma (PPP)is centrifugally separated from PRP in the second stage 26. Duringprocessing, PPP is conveyed from the second stage 26 through the port36, leaving PC in the second stage 26.

Tubing 210 communicates with the PPP port 36. The tubing 210 includes afirst branch 212, which leads (via an in line pump 214) to a collectioncontainer 216. During the platelet collection stage of processing, adesignated volume of the PPP is retained in the container 216 foreventual use as a suspension medium for the PC. Following theplatelet-collection stage of the process, a suspension stage is begun,during which all or a portion of the PPP in the container 216 isconveyed back into the second stage 26, via tubing branch 218, tosuspend the PC for storage and transfusion.

The tubing 210 also includes a second branch 220, which leads to thedonor. The second branch 220 conveys the remaining volume of PPP (i.e.,the portion not designated for use as a suspension medium) for return tothe donor during processing.

For a system configured as shown in FIG. 15, the platelet-poor plasmabaseline T(PPP) can be derived for the individual donor in various ways.

For example, the value of T(PPP) can be obtained empirically by plottingthe fluctuation of T(PRP) over time during a series of processingperiods using a given system, and by ascertaining when the value ofT(PRP) obtained during the platelet collection stage matches the valueof T(PPP) obtained during a suspension stage. FIG. 16 shows arepresentative plot of the fluctuation of T(PRP) over time during atypical platelet collection stage and suspension stage, using acentrifugal blood collection system of the type previously described andillustrated. In FIG. 16, T(PRP) is expressed as a raw digital numbersignal from the diode detector 206, so that the digital number increaseswith sensed opacity (as before described, between 0 and 2048). The valueA represents T(SAL) obtained during a set up stage, as describedearlier. The opacity is seen to rise as the platelet collection stageprogresses, until a desired constituency of PRP is obtained, under thecontrol of the interface controller 12, as previously described. Thevalue B represents a running average of T(PRP) obtained during theplatelet collection stage. The value C represents T(PPP) obtained duringthe suspension stage. FIG. 16 shows that a corresponding value D,essentially equal to T(PPP) is sensed during the early stages (of theplatelet collection stage (e.g., after about 3 minutes, as saline isprogressively replaced by PRP). Empirical results demonstrate that, fora given procedure on a given system, the value D, corresponding toT(PPP), consistently occurs after the conveyance of a certain volume ofPRP from the first stage 24 during the platelet collecting stage (whichin FIG. 16, is about 58 ml). Based upon such empirical data, T(PPP) canbe obtained by measuring T(PRP) at a designated point in the plateletcollection procedure and assigning T(PPP) its value. It has beenempirically determined that the point in the platelet collectionprocedure where T(PPP) can be accurately obtained in this fashion occurswhen priming fluid is first cleared from the first stage 24 and tubing104, which volume is designated V_(INI). This initial processing volumeV_(INI) is also used in by the. processing element 202 in deriving theintegrated PCI value, as will be described below.

The intensity value T(PPP) assigned in the above described way can beassumed to remain constant for the remainder of the procedure, unlessthe donor's plasma carries a very high transient dietary lipid content.

Alternatively, the value of T(PPP) can be obtained or updated during theplatelet collection stage by suspending normal PRP processing andcirculating a known volume of PPP from the second stage 26 via the pump214, through the tubing 218, and into tubing 104 upstream of the opticalmonitor 204. The baseline T(PPP) is then derived according to Equation4A.

In the illustrated embodiment, T(PPP) is sampled at a set sample rate,e.g., once every five seconds. A series of readings T(PPP) are takenover a set sampling period (e.g., 5 samples) and are averaged to obtainan average T(PPP), which the processing element 202 assigns as the valuefor T(PPP).

The baseline T(PPP) can be obtained in this fashion at any time duringthe procedure. However, T(PPP) preferably obtained in this fashion aftera sufficient volume of whole blood has been processed to bring thesystem into a steady state processing condition, e.g., after more than500 ml of whole blood have been processed. The volume of PPP that needsto be circulated to accurately obtain T(PPP) can be empiricallydetermined. In the illustrated arrangement, the circulation of about 15to 20 ml of PPP is required for the optical monitor 204 to reach anoptical steady state value for T(PPP).

A value for T(PPP) can be obtained at the outset of processing, when theprocessed plasma volume reaches V_(INI), as described above. It can thenbe updated later in the procedure after steady state processingconditions occur by suspending PRP processing and circulating a volumeof PPP past the optical monitor 204, as also described above.

(iv) Deriving Platelet Volume Collected

The processing element 202 numerically integrates the T(PRP) relative toT(PPP) during the processing period relative to the plasma volume V_(p)processed, to derive the volume of platelets collected, or PCI.

There are various ways in which this numeric integration can beaccomplished. In a preferred implementation, the processing element 202computes PCI as follows: $\begin{matrix}{{PCI} = {{\sum\limits_{V}}_{INI}^{V_{PRP}}{\left\lbrack {1 - \frac{T({PRP})}{T({PPP})}} \right\rbrack \Delta \quad V_{PRP}}}} & (6)\end{matrix}$

where:

V_(INI) represents the volume of plasma that must be processed beforepriming fluid is cleared from the first stage 24 and tubing 104, earlierdescribed.

V_(PRP) is the total volume of PRP collected during the procedure.

ΔV_(PRP) is the incremental plasma volume (in ml) processed during asample interval(n). ΔV_(PRP) can be expressed as a function of thesampling rate and plasma pump rate, as follows:

ΔV _(PRP) =Q _(p(n)) Δt _((n))

where:

Q_(p(n)) represents the flow rate of plasma (in ml/min) through thetubing 104 when T(PRP) is measured (which is controlled by the pump110), and

Δt_((n)) is the period of the sample interval (or the sampling rate),expressed as a fraction of one hour, e.g., a sample period of once every5 seconds represents the fraction {fraction (1/12)}.

By assuming T(PPP), when ascertained, to be constant through a givenprocedure, Equation (6) can be reduced to the following expression:$\begin{matrix}{{PCI} = {\left( {V_{PRP} - V_{INI}} \right) - {\frac{1}{T({PPP})}{{\sum\limits_{V}}_{INI}^{V_{PRP}}{{T({PRP})}\Delta \quad V_{PRP}}}}}} & \text{(6A)}\end{matrix}$

FIG. 17 shows a plot of 358 values of PCI derived during bloodseparation processes of the type previously described, performed byfifteen different centrifuges of the type previously described. Thevalues of PCI are plotted against associated platelet volumes collected(in ml), which are derived by multiplying the number of plateletscollected by their mean platelet volume (MPV), as measured by an offline counter. The plot shows a linear distribution having the followingrelationship:

PLT _(Vol)(ml(=0.24+0.0070PCI

where 0.24 is the y-intercept, which is only about 6% of the nominalexpected collected platelet volume of 4.0×10¹¹ ml, and 0.0070 is theslope of the plot. The linear distribution has an r² value of 0.75. FIG.17 demonstrates that a good correlation exists between PCI and collectedplatelet volume PLT_(Vol).

FIG. 18 shows a plot of the same 358 values of PCI against associatedplatelet yields PLT_(Yld) (expressed in units×10¹¹), which are derivedby multiplying the platelet count (measured by an off line counter) bythe volume of platelet concentrate. The plot shows a linear distributionhaving the following relationship:

PLT _(Ylt)(x10¹¹)=0.67+0.0080PCI

where the y-intercept of 0.67 is 17% of the nominal expected collectedplatelet volume of 4.0×10¹¹ ml. The linear distribution has an r² valueof 0.70. FIG. 17 demonstrates that a correlation also exits between PCIand platelet yields, but also illustrates that the quantity PCI is moreindicative of platelet volume PLT_(Vol) than the number of plateletscollected PLT_(Yld).

(2) Second Utility Function F2

The second utility function F2 includes a processing element 224 whichreceives as input the calculation of PCI made by the first utilityfunction F1. Based upon the value of PCI, the processing element 224derives the optimum storage conditions to sustain the platelet volumecollected during the expected storage period. The processing element 224generates an output reflecting the number of preselected storagecontainers required for the platelets Plt_(Bag) and the volume of plasma(PPP) Plt_(Med) (in ml) to reside as a storage medium with theplatelets.

The optimal storage conditions for platelets depends upon plateletvolume desired to be stored Plt_(Vol). As demonstrated above, the valueof PCI (in ml) correlates with Plt_(Vol). Therefore, the platelet volumePltv_(Vol) can be accurately expressed in terms of PCI, without the needto know the actual platelet yield or to independently assess plateletcell counts or mean platelet volumes (MPV).

As the value of PCI increases, so too does the platelets' demand foroxygen during the storage period. As the value of PCI increases, theplatelets' glucose consumption to support metabolism and the generationof carbon dioxide and lactate as a result of metabolism also increase.The physical characteristics of the storage containers in terms ofsurface area, thickness, and material are selected to provide a desireddegree of gas permeability to allow oxygen to enter and carbon dioxideto escape the container during the storage period.

The plasma storage medium contains bicarbonate HCO₃, which buffers thelactate generated by platelet metabolism, keeping the pH at a level tosustain platelet viability. As the value of PCI increases, the demandfor the buffer effect of HC0 ₃, and thus more plasma volume duringstorage, also increases.

A. Deriving Plt_(Bag)

The partial pressure of oxygen PO₂ (mmHg) of platelets stored within astorage container having a given permeation decreases in relation to thetotal platelet volume Plt_(Vol) the container holds. FIG. 19 is a graphbased upon test data showing the relationship between PO₂ measured afterone day of storage for a storage container of given permeation. Thestorage container upon which FIG. 19 is based has a surface area ofabout 54 in² and a capacity of 1000 ml. The storage container has apermeability to O₂ of 194 cc/100 in²/day, and a permeability to CO₂ 1282cc/100 in²/day.

When the partial pressure PO₂ drops below 20 mmHg, platelets areobserved to become anaerobic, and the volume of lactate byproductincreases significantly. FIG. 19 shows that the selected storagecontainer can maintain PO₂ of 40 mmHg (well above the aerobic region) atPlt_(Vol)≦4.0 ml. On this conservative basis, the 4.0 ml volume isselected as the target volume Plt_(TVol) for this container. Targetvolumes Plt_(TVol) for other containers can be determined using thissame methodology.

The processing element 224 uses the target platelet volume Plt_(TVol) tocompute Plt_(Bag) as follows: $\begin{matrix}{{BAG} = \frac{a + {bPCI}}{{Plt}_{TVol}}} & (8)\end{matrix}$

where:

a is the y-intercept and b is the slope of the plot between PLT_(Vol)and PCI derived by linear regression analysis, as previously describedand shown in FIG. 17. The values of a and b will change according to theoperating parameters of the particular blood processing system. In theillustrated embodiment a=0.24 and b=0.0070, and

where Plt_(Bag) is the number of storage containers required, and

Plt_(Bag)=1 when BAG ≦1.0, otherwise

Plt_(Bag)=[BAG+1], where [BAG+1]

is the integer part of the quantity BAG+1.

For example, based upon the systems upon which FIG. 17 is derived, givena value of PCI=400 ml (which correlates to a Plt_(Vol)=3.8 ml), andgiven Plt_(TVol)=4.0 ml, BAG=0.95, and Plt_(Bag)=1. Based upon thesystems upon which FIG. 17 is derived, if the value of PCI=600 ml (whichcorrelates to a Plt_(Vol)=4.4 ml), BAG=1.1 and Plt_(Bag)=2.

When Plt_(Bag)>1, the quantity a+b(PCI) is divided equally among thenumber of containers called for.

B. Deriving Plt_(Med)

The amount of bicarbonate used each day is a function of the storagethrombocytocrit Tct (%), which can be expressed as follows:$\begin{matrix}{{Tct} = \frac{{PLT}_{Vol} \times {MPV}}{{Plt}_{Med}}} & (9)\end{matrix}$

The relationship between bicarbonate HCO₃ consumption per day and Tctcan be empirically determined for the selected storage container. FIG.20 shows a graph showing this relationship for the same container thatthe graph in FIG. 19 is based upon. The y-axis in FIG. 20 shows theempirically measured consumption of bicarbonate per day (in Meq/L) basedupon Tct for that container. The processing element 224 includes thedata expressed in FIG. 20, for example, in a look-up table 226.

The processing element 224 derives the anticipated decay of bicarbonateper day over the storage period ΔHCO₃ as follows: $\begin{matrix}{{\Delta \quad {HCO}_{3}} = \frac{{Don}_{{HCO}_{3}}}{Stor}} & (10)\end{matrix}$

where:

Don_(HCO3) is the measured bicarbonate level in the donor's blood(Meq/L), or alternatively, is the bicarbonate level for a typical donor,which is believed to be 19.0 Meq/L ±1.3, and

Stor is the desired storage interval (in days, typically between 3 to 6days).

Given ΔHCO₃, the processing element 224 derives Tct from the look-uptable 226 for selected storage container. For the storage container uponwhich FIG. 20 is based, a Tct of about 1.35 to 1.5% is believed to beconservatively appropriate in most instances for a six day storageinterval.

Knowing Tct and PCI, the utility function F2 computes Plt_(Med) basedupon Eq (8), as follows: $\begin{matrix}{{Plt}_{Med} = \frac{a + {bPCI}}{\frac{Tct}{100}}} & (11)\end{matrix}$

where Tct can be a value based upon empirical data for the particularstorage container (as just described and shown in FIG. 20), and notrequiring off line counting or sizing techniques.

When Plt_(Bag)>1, Plt_(Med) is divided equally among the number ofcontainers called for.

(3) The Third Processing Function (F3)

The third utility function F2 includes a processing element 324 whichreceives as input the calculation of PCI made by the first utilityfunction F1. Based upon the value of PCI, the processing element 324derives the amount of whole blood that needs to be processed in orderfor a the procedure to collect a desired yield of platelets, calledWB_To_Process.

The third utility function F3 is activated after the volume of plasmaprocessed equals V_(INI), earlier described. The third utility functionF3 continues to run for the remainder of the process. WB_To_Process canbe updated whenever new values of T(PRP) or T(PPP) are acquired toprovide an updated PCI or periodically at prescribed processingintervals, e.g., after every 500 ml of whole blood processed.

In the illustrated embodiment, the operator inputs a desired plateletyield, or PltGoal. The processing element 324 derives a targeted PCIvalue, called PCI_(Targeted), as a function of Plt_(Goal). The functionis derived empirically based upon a series of blood processingprocedures conducted to correlate PCI against actual platelet yields,which have been previously described in terms of the linear regressionanalyses shown in FIGS. 17 or FIG. 18. The function also preferablytakes into account a counter calibration factor, which brings the dataderived on line during the series of blood processing procedures intoconformance with date derived off line by use of a platelet counter. Thecounter calibration factor varies according to the type and manufacturerof the particular off line platelet counter used. The operator is givena table of counter calibration factors and instructed to input thefactor that corresponds to the off line platelet counter that theoperator uses.

In a preferred embodiment, the function relating PCI_(Target) toPlt_(Goal) is expressed as follows: $\begin{matrix}{{PCI}_{Target} = \frac{C_{1}{Plt}_{Goal}}{C_{2}}} & (12)\end{matrix}$

Where:

C₁ is a factor derived by analysis of blood processing data, aspreviously described and shown in FIG. 17 or FIG. 18. In arepresentative implementation, C₁ will typically lay in a numericalrange of between 100 and 115, based upon the results of the bloodprocessing procedures upon which the analysis is based. In a current,preferred embodiment using an Amicus™ Blood Processing System (BaxterHealthcare Corporation), C₁=112.5.

C₂ is the counter calibration factor prescribed for the off-lineplatelet counter in use.

In the illustrated embodiment, when the processed plasma volume equalsV_(INI), the processing element 324 derives an initial baseline T(PPP),as previously described. The processing element 324 also begins toderive T(PRP) every five seconds, as also previously described. A finalbaseline T(PPP) is derived later in the procedure, and this value isused throughout subsequent processing as T(PPP).

The processing element 324 derives a quantity called Sigma, where:

Sigma=T(PRP)*Q _(p) Δt(13)

where

T(PRP) is the transmission of PRP measured by the optical detectormeasured at the end of a sample interval (n),

Q_(p) represents the flow rate of plasma (in ml/min) through the tubing104 when T(PRP) is obtained, and

Δt is the period of the sample interval (or the sampling rate),expressed as a fraction of one hour, e.g., a sample period of once every5 seconds represents the fraction {fraction (1/12)}.

The processing element 324 initializes Sigma at zero, Sigma_(Old). Oncethe amount of plasma processed equals V_(INI), the processing element324 measures T(PRP)and derives a current Sigma at the prescribedsampling rate. For each sampling period, the new value for Sigma isadded to the old value of Sigma, to yield an integrated current valuefor Sigma (Sigma_(current))

At the end of each sampling period, the processing element 324 derives acurrent PCI value (PCI_(current)), as follows:${PCI}_{Current} = {\left( {V_{{PRP}{({Current})}} - V_{INI}} \right) - \left( {\frac{1}{T({PPP})}*{Sigma}_{Current}} \right)}$

where:

V_(PRP(Current)) is the current cumulative volume of PRP processed atthe end of the given sampling period.

At the end of each sampling period, the processing element 324 alsoderives a current value for WB_To_Process as follows: $\begin{matrix}{{{WB}_{—}{To}_{—}{Process}} = {{\left( {{{WB}_{—}{Processed}} - V_{Prime}} \right)*\left\lbrack \frac{{PCI}_{Target}}{{PCI}_{Current}} \right\rbrack} + V_{Prime}}} & (14)\end{matrix}$

where:

WB_Processed is the volume of whole blood that has been processed up tothe present point of the process, and

V_(Prime) is the priming volume of the blood processing flow path.

The WB_To_Process is preferably displayed for viewing by the operator onan appropriate user interface screen (not show). The displayedWB_To_Process value can be updated periodically, e.g., for every 100 mlof whole blood processed. The operator can be given the option ofaltering the WB_To_Process value in real time during the course of agiven procedure. In this circumstance, the altered value is accepted andcorrected to get the desired platelet yield.

Various features of the inventions are set forth in the followingclaims.

We claim:
 1. A blood processing system comprising an input to receive avalue indicating a desired platelet volume, a separation chamberassembly operating to separate blood into constituents including aplasma constituent containing platelets and having an optical density,an outlet path for conveying a volume of the plasma-constituent from theseparation chamber during a processing period, the volume of plasmaconstituent containing a platelet volume, a sensor assembly operating todetect the optical density of the plasma constituent in the outlet pathduring several sample intervals within the processing period andgenerate for each sample interval a sampled opacity value expressing thedetected optical density as a function of incremental plasma volumeprocessed during the respective sample interval, a first processingelement coupled to the sensor including an element that is operable tosum the sampled opacity values over the processing period and generatean integrated opacity value output, and a second processing elementwhich receives as input the integrated opacity value output andgenerates a second output based, at least in part, upon the integratedopacity value output, comprising a value indicating a blood volume thatneeds be processed to obtain the desired platelet volume.
 2. A systemaccording to claim 1 wherein the first processing element includes anoutput that expresses the platelet volume based upon the integratedopacity value output.
 3. A system according to claim 1 wherein theseparation chamber further separates the plasma constituent into aplatelet-poor plasma constituent and a platelet concentrate comprisingthe platelet volume, the platelet-poor plasma constituent including anoptical density that varies with lipid content, further including asensor to detect the optical density of the platelet-poor plasmaconstituent and generate a baseline optical density value, and whereinthe first processing element includes a calibration element thatcalibrates the integrated opacity value output against the baselineoptical density value.
 4. A system according to claim 1 and furtherincluding a third processing element which receives as input theintegrated opacity value output and generates a third output, differentthan the second output, based, at least in part, upon the integratedopacity value output.
 5. A system according to claim 4 wherein the thirdoutput comprises a parameter for storing the desired platelet volume. 6.A system according to claim 4 wherein the third output includes a valuerepresenting a number of selected storage containers to be used for thedesired platelet volume.
 7. A system according to claim 4 wherein thethird output includes a value representing a recommended volume ofstorage medium for the desired platelet volume.
 8. A system according toclaim 1 wherein the sensor includes an emitter of a selected wavelengthof light energy and a detector of the selected wavelength.
 9. A systemaccording to claim 8 wherein the sampled opacity value is free of sidescatter effects.
 10. A blood processing method comprising defining adesired platelet volume, separating blood into constituents including aplasma constituent containing platelets and having an optical density,conveying in an outlet path a volume of the separated plasma constituentduring a processing period, the volume of separated plasma constituentcontaining a platelet volume, detecting the optical density of theplasma constituent in the outlet path during several sample intervalswithin the processing period, generating for each sample interval asampled opacity value expressing the detected optical density as afunction of incremental plasma volume processed during the respectivesample interval, generating an integrated opacity value output bysumming the sampled opacity values over the processing period,generating an output based, at least in part, upon the integratedopacity value output, comprising a value indicating a blood volume thatneeds be processed to obtain the desired platelet volume.
 11. A methodaccording to claim 10 further including expressing the platelet volumebased upon the integrated opacity value output.
 12. A method accordingto claim 10 wherein the separating step provides a platelet-poor plasmaconstituent which includes an optical density that varies with lipidcontent, further including the steps of detecting the optical density ofthe platelet-poor plasma constituent and generating a baseline opticaldensity value and calibrating the integrated opacity value outputagainst the baseline optical density value.
 13. A method according toclaim 10 and further including the step of generating another outputbased, at least in part, upon the integrated opacity value output.
 14. Amethod according to claim 13 wherein the another output comprises aparameter for storing the desired platelet volume.
 15. A methodaccording to claim 10 wherein the step of generating the sampled opacityvalues is free of side optical scatter effects.